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Association of cholinergic basal forebrain volume and functional connectivity with markers of inflammatory response in the Alzheimer’s disease spectrum

Teipel, S, Bruno, D and Heneka, M Association of cholinergic basal forebrain volume and functional connectivity with markers of inflammatory response in the Alzheimer’s disease spectrum. Journal of Alzheimer's Disease. ISSN 1387-2877 (Accepted)

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Abstract

Background: Inflammation has been described as a key pathogenic event In Alzheimer’s disease (AD), downstream of amyloid and tau pathology. Preclinical and clinical data suggest that the cholinergic basal forebrain may moderate inflammatory response to different pathologies. Objective: To study the association of cholinergic basal forebrain volume and functional connectivity with measures of neuroinflammation in people from the AD spectrum Methods: We studied 261 cases from the DELCODE cohort, including people with subjective cognitive decline, mild cognitive impairment, AD dementia, first degree relatives and healthy controls. Using Bayesian ANCOVA, we tested associations of MRI indices of cholinergic basal forebrain volume and functional connectivity with CSF levels of sTREM2 as a marker of microglia activation, and serum levels of complement C3. Using Bayesian elastic net regression, we determined associations between basal forebrain measures and a large inflammation marker panel from CSF and serum. Results: We found anecdotal to moderate evidence in favor of the absence of an effect of basal forebrain volume and functional connectivity on CSF sTREM2 and serum C3 levels both in Aβ42/ptau-positive and negative cases. Bayesian elastic net regression identified several CSF and serum markers of inflammation that were associated with basal forebrain volume and functional connectivity. The effect sizes were moderate to small. Conclusion: Our data-driven analyses generate the hypothesis that cholinergic basal forebrain may be involved in the neuroinflammation response to Aβ42 and phospho-tau pathology in people from the AD spectrum. This hypothesis needs to be tested in independent samples.

Item Type: Article
Uncontrolled Keywords: 1103 Clinical Sciences, 1109 Neurosciences, 1702 Cognitive Sciences
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Psychology (new Sep 2019)
Publisher: IOS Press
Date Deposited: 17 Dec 2021 13:21
Last Modified: 17 Dec 2021 13:30
URI: https://researchonline.ljmu.ac.uk/id/eprint/15939

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